A task-focused approach to evaluating molecular clocks that estimate biological aging

A narrative review proposes a framework for evaluating molecular aging clocks based on four specific tasks.

• Biological age estimation often relies on mean absolute error (MAE) against chronological age, which may not fully capture clinical relevance.
• The proposed framework organizes applications of aging clocks into tasks: estimating chronological age, assessing age-independent deviation, predicting future disease or mortality risk, and monitoring aging pace or intervention response.
• For each task, the framework identifies necessary components such as target construct, output, preprocessing, validation metrics, and interpretation limits.
• A four-layer model categorizes molecular measures into stable measures, pace-of-aging indicators, dynamic functional markers, and organ-specific vulnerabilities.
• Evaluating aging clocks as task-specific tools emphasizes the importance of calibration, discrimination, reliability, transportability, uncertainty, and incremental value.

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